Few people had a worse time in space than the crew of Apollo VII. It wasn’t just the 11 days they spent in orbit in 1968 test-driving the new — and decidedly cramped — Apollo command module. That’s what they’d trained for, after all. What they hadn’t banked on was that they’d all contract serious head colds — first Wally Schirra, the veteran commander, then his rookie crewmates Walt Cunningham and Donn Eisele. All three men grew cranky, snappish and downright mutinous, even breaking mission rules by refusing to wear their helmets during re-entry, lest their already clogged ears pop painfully. Schirra, who had announced in advance that Apollo VII would be his last mission, retired and went on to become a pitchman for, yes, the cold medicine Actifed. Cunningham and Eisele, who had been in line for flights to the moon, were permanently grounded.

In many ways, NASA got lucky that an Apollo VII happened only once. If you were trying to design a friendlier Petri dish for infectious agents, you couldn’t do better than a spacecraft — a confined space in which densely packed humans breathe recirculated air, touch common surfaces over and over again and have a whole lot less opportunity to wash than they do on Earth. The risk becomes worse as NASA contemplates renewed flights to deep space where medical care is even farther out of reach than it is when crews are in orbit.

“Two years in a microgravity environment may have profound changes in astronauts and in aggressive microbes,” says infectious disease specialist Dr. Leonard Mermel of Brown University and Rhode Island Hospital, “creating a scenario not previously experienced in the history of human space flight.” To prevent that from happening, Mermel, in consultation with NASA, has just published a paper in the journal Clinical Infectious Diseases exploring what steps we need to take to make space a healthier place — and what the perils are if we don’t.

Mermel began his work by surveying the health records of astronauts across the 30 year history of the space shuttle program, and the results were troubling. Of 106 flights and 742 crewmembers he studied, there were 29 cases of infectious disease transmission. Most of them involved fever and chills, but there were also cases of fungal, urinary tract and skin infections, as well as flu-like illnesses and viral gastroenteritis.

A lot of the problem begins with zero-g — which is something of a Disneyland for germs. A cough or sneeze on Earth blasts infectious particles from 3 to 6 ft. (1 to 2 m) away before gravity takes over and they fall out of the air. In space, they float everywhere. When they do land, they don’t settle in some safe, out of the way place, because in a spacecraft there is no out of the way. Instrument panels, food preparation surfaces, experiment racks are everywhere. And astronauts who do become infected, are often less up to fighting the pathogen than they normally would be.

For reasons scientists have not quite figured out, the immune system can go on the fritz in space: wounds heal more slowly; infection-fighting T-cells send signals less efficiently; bone marrow replenishes itself less effectively; killer cells — another key immune system player — fight less energetically. At the same time, the pathogens grow stronger, developing thicker cell walls, greater resistance to antimicrobial agents and a greater ability to form so-called biofilms that cling to surfaces. Dormant herpesvirus infections are known to become more active in space, and swabs of astronauts taken when they return to Earth show higher populations of staph on the skin, in the upper airway and in the colon. All of that means a single spark of a disease could burn out of control fast.

“Oy vey,” Mermel says straightforwardly when contemplating all of the ways disaster could strike. “What if someone started shedding a streptococcus that quickly spread to others? Another scenario would be a reactivation of a dormant bacteria like meloidosis that would cause pneumonia and spread.” Even worse, a dormant salmonella infection from one astronaut could reawaken and infect food as it’s being prepared.

Simple air filtration systems seem like they ought to cut the risk, but there are problems. So-called high-efficiency particulate air (HEPA) filters, regularly used in medical settings, are energy hogs and would not fit into the limited power budget of a spacecraft. Irradiation of all food is a common way to kill microbes before they’re consumed, but the human gut needs some symbiotic bacteria to function properly and wiping them all out could make astronauts sicker than they’d be if you just left things alone. And while humidity is controlled in a spacecraft for both comfort and equipment safety, it’s not yet regulated with pathogen suppression in mind.

“We do know on Earth that humidity has a major effect on influenza virus and it may explain greater transmission in heated buildings with lower humidity,” says Mermel. “I don’t know if anyone’s studied these variables [in space].”

That kind of research is essential to safeguard future astronauts, as is the fast-track design of higher efficiency HEPA systems. Mermel also calls for a host of other measures including the use of what’s known as positive or neutral air pressure systems to keep atmosphere — and germs — carried up in unmanned cargo vessels from flowing into manned vessels like the International Space Station. He recommends that the interior surfaces of all living and working spaces be covered in non-porous antimicrobial material, and that washing stations and toilets be redesigned so they can be operated by foot pedals. Better screening and vaccinating of astronauts before missions is essential too — especially as multi-nation crews mix pathogens that may be familiar to one astronaut but novel to another. “This adds a unique twist,” Mermel says, “[involving] what to screen for and what might rear its head several months after launch.”

None of these measures could guarantee astronauts won’t get sick in space — but nothing guarantees people won’t get sick on Earth either. On Earth, however, you can always duck out to the doctor. When you’re 150 million miles from home and a year or two from an emergency room or a drug store, it pays to take a couple of precautions.